rs2057687

Variant names:

• chr5-132551553-C-T
• rs2057687
• ENST00000638452.2:c.-168-7731C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000638452.2(ENSG00000283782):​c.-168-7731C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 139,976 control chromosomes in the GnomAD database, including 12,141 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.39 (12141 hom., cov: 31)
• Consequence: ENSG00000283782 ENST00000638452.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.960
• Publications: 7 publications found

Genes affected

ENSG00000283782 (HGNC:):

IL5 (HGNC:6016): (interleukin 5) This gene encodes a cytokine that acts as a growth and differentiation factor for both B cells and eosinophils. The encoded cytokine plays a major role in the regulation of eosinophil formation, maturation, recruitment and survival. The increased production of this cytokine may be related to pathogenesis of eosinophil-dependent inflammatory diseases. This cytokine functions by binding to its receptor, which is a heterodimer, whose beta subunit is shared with the receptors for interleukine 3 (IL3) and colony stimulating factor 2 (CSF2/GM-CSF). This gene is located on chromosome 5 within a cytokine gene cluster which includes interleukin 4 (IL4), interleukin 13 (IL13), and CSF2 . This gene, IL4, and IL13 may be regulated coordinately by long-range regulatory elements spread over 120 kilobases on chromosome 5q31. [provided by RefSeq, Jul 2013]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000638452.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000283782	ENST00000638452.2	TSL:5	c.-168-7731C>T		intron	N/A	ENSP00000492349.2	A0A1W2PQ90
	ENSG00000283782	ENST00000638568.2	TSL:5	c.-310-4779C>T		intron	N/A	ENSP00000491158.2	A0A1W2PQ90
	ENSG00000283782	ENST00000640655.2	TSL:5	c.-168-7731C>T		intron	N/A	ENSP00000491596.2	A0A1W2PQ90

Frequencies

GnomAD3 genomes AF: 0.393 AC: 55042 AN: 139884 Hom.: 12139 Cov.: 31

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.426

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.454

Gnomad MID AF: 0.435

Gnomad NFE AF: 0.481

Gnomad OTH AF: 0.384

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.393 AC: 55042 AN: 139976 Hom.: 12141 Cov.: 31 AF XY: 0.395 AC XY: 27071 AN XY: 68490

African (AFR) AF: 0.155 AC: 4698 AN: 30280

American (AMR) AF: 0.491 AC: 7311 AN: 14902

Ashkenazi Jewish (ASJ) AF: 0.439 AC: 1519 AN: 3458

East Asian (EAS) AF: 0.141 AC: 725 AN: 5152

South Asian (SAS) AF: 0.452 AC: 2170 AN: 4806

European-Finnish (FIN) AF: 0.454 AC: 4742 AN: 10440

Middle Eastern (MID) AF: 0.430 AC: 122 AN: 284

European-Non Finnish (NFE) AF: 0.481 AC: 32593 AN: 67718

Other (OTH) AF: 0.382 AC: 777 AN: 2032

Alfa AF: 0.390 Hom.: 1695

Bravo AF: 0.350

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.4
DANN	Benign	0.36
PhyloP100		-0.96

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2057687;

hg19: chr5-131887245;